1,5-Dideoxy-1,5-imino-D-glucitol(deoxynojirimycin) and derivatives thereof are known antihyperglycemic agents and antiviral compounds. These compounds and methods for their preparation and uses are disclosed in U.S. Pat. Nos. 4,849,430--Fleet et al, Method of Inhibiting Virus; 4,182,767--Murai et al, Antihyperglycemic N-Alkyl-3,4,5-trihydroxy-2-piperidine Methanol; 4,639,436--Junge, et al, Antidiabetic 3,4,5-Trihydroxypiperidines; 4,220,782--Stoltefuss, Preparation of 1-Desoxynojirimycin and N-Substituted Derivatives; and 4,429,117 - Koebernick et al, Process for the Production of Known and New 6-Amino-6-desoxy-2,3-O-isopropylidene-.alpha.-L-sorbofuranose Derivatives, and Intermediate Products of the Process.
Acquired immune deficiency syndrome, (AIDS), is a serious disease. As a consequence, a great effort is being made to develop drugs and vaccines to combat AIDS. The AIDS virus, first identified in 1983 has been described by several names and is currently referred to as human immunodeficiency virus (HIV). Two distinct AIDS viruses, HIV-1 and HIV-2, have been described. HIV-1 is the virus originally identified in 1983 by Montagnier and co-workers at the Pasteur Institute in Paris [Ann. Virol. Inst. Pasteur 135 E, 119-134 (1984)], while HIV-2 was more recently isolated by Montagnier and his co-workers in 1986 [Nature 326, 662-669 (1987)]. As used herein, HIV is meant to refer to these viruses in a generic sense.
Development of an AIDS vaccine is hampered by lack of understanding of mechanisms of protective immunity against HIV, the magnitude of genetic variation of the virus, and the lack of effective animal models for HIV infection. See, for example, Koff and Hoth, Science 241, 426-432 (1988).
The first drug to be approved by the U.S. Food and Drug Administration (FDA) for treatment of AIDS was zidovudine, better known under its former name, azidothymidine (AZT). Chemically, this drug is 3'-azido-3'deoxythymidine. This drug was originally selected as a potential weapon against AIDS because it was shown to inhibit replication of the virus in vitro. Such in vitro tests are useful and virtually the only practical method of initially screening and testing potential anti-AIDS drugs. A serious drawback of AZT, however, is its toxic side-effects. Thus, the search for better anti-AIDS drugs continues.
The HIV inhibitory activity of 1,5-dideoxy-1,5-imino-D-glucitol (deoxynojirimycin) and its N-methyl derivative is disclosed in PCT Inter. Appln. 87/03903, published Jul. 2, 1987. The substantially more effective anti-HIV activity of the N-butyl derivative of deoxynojirimycin is disclosed in U.S. Pat. No. 4,849,430.
U.S. Pat. No. 4,220,782 describes a process for producing 1-deoxy-nojirimycin and its N-substituted derivatives, using two different starting materials, one of which is N-substituted 6-amino-2,3-O-isopropylidene-6-deoxy-.alpha.-L-sorbofuranose. The starting material is deblocked by treatment with a strong mineral acid which yields an ammonium salt. The salt is isolated and then hydrogenated.